Histone Deacetylase-2 Serves as an Independent Prognostic Indicator in Osteosarcoma

Abstract

Background Osteosarcoma is the most common primary malignant tumor of skeleton in adolescence. Histone deacetylase 2 (HDAC2), a member of class I histone deacetylase, is putatively involved in tumorigenesis of human malignancies. This study aimed to evaluate the expression pattern and prognostic value of HDAC2 in osteosarcoma.Methods Four datasets were obtained from the gene expression omnibus (GEO) database to explore the expression and prognostic value of HDAC2. Level 3 mRNA expression profiles and clinical data were obtained in The Cancer Genome Atlas (TCGA) for validation. Expression pattern of HDAC2 were illustrated in GSE16088, GSE36001 and GSE42352. The prognostic value of HDAC2 was evaluated and validated by Kaplan-Meier analyses, receiver operating characteristic (ROC), concordance index (C-index) and calibration curve in GSE21257 and TCGA. Multivariate Cox regression analysis, nomogram, and decision curve analysis (DCA) were performed to assess the prognosis predictive capability. Protein-protein interaction (PPI) and gene set enrichment analysis (GSEA) were applied to further understand the molecular network and regulatory mechanisms.Results HDAC2 expression was significantly increased in osteosarcoma tissues. High HDAC2 expression was associated with tumor metastasis and chemotherapy efficacy. Kaplan-Meier analysis demonstrated that high HDAC2 predicted worse overall survival. The ROC curve showed good performance in survival prediction. Cox regression demonstrated that HDAC2 could be an independent prognostic indicator. GSEA revealed patients with high HDAC2 expression were enriched with multiple ontological signatures.Conclusions Elevated expression of HDAC2 may identify an aggressive subgroup in osteosarcoma and serve as an independent prognostic indicator in these patients.